20-963960-A-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001029871.4(RSPO4):c.570T>G(p.Cys190Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,956 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001029871.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RSPO4 | NM_001029871.4 | c.570T>G | p.Cys190Trp | missense_variant | Exon 4 of 5 | ENST00000217260.9 | NP_001025042.2 | |
RSPO4 | XM_017027839.2 | c.570T>G | p.Cys190Trp | missense_variant | Exon 4 of 4 | XP_016883328.1 | ||
RSPO4 | NM_001040007.3 | c.409+3214T>G | intron_variant | Intron 3 of 3 | NP_001035096.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249428Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135352
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461716Hom.: 1 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727168
GnomAD4 genome AF: 0.000145 AC: 22AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74438
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.570T>G (p.C190W) alteration is located in exon 4 (coding exon 4) of the RSPO4 gene. This alteration results from a T to G substitution at nucleotide position 570, causing the cysteine (C) at amino acid position 190 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at